Glass Ceiling Commission - The Impact of the Glass Ceiling and Structural Change on Minorities and Women

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Quantitative speech production profiles and focal left hemisphere lesion

The clinical differentiation between apraxia of speech (AOS) and aphasia with phonemic paraphasia is based on impressionistic consideration of a varying list of speech properties. The diagnosing clinician is challenged with determining the presence or absence of these disorders by considering the extent to which characteristic features are evident in the speech output and by determining how much relative weight to assign to each. Predictably, the subjective nature of the diagnostic process can translate to limited agreement, even among experienced clinicians (Haley, Jacks, de Riesthal, Abou-Khalil, & Roth, 2012), and the risks of misdiagnosis and diagnostic uncertainty are substantial (Wambaugh, 2006). Additionally it is likely that the adherence to a strictly dichotomous classification system overlooks theoretically and clinically important heterogeneity. The purpose of this study was to identify a preliminary set of speech production profiles based on naturally occurring variations in individuals with acquired focal brain lesions. To avoid classification circularity, assessments were conducted without consideration of clinical speech diagnosis, and metrics were selected to represent diverse and robust observations about speech properties associated with left hemisphere lesions

Astro2020 Science White Paper: Synoptic Studies of the Sun as a Key to Understanding Stellar Astrospheres

Ground-based solar observations provide key contextual data (i.e., the 'big picture') to produce a complete description of the only astrosphere we can study in situ: our Sun's heliosphere. The next decade will see the beginning of operations of the Daniel K. Inouye Solar Telescope (DKIST). DKIST will join NASA's Parker Solar Probe and the NASA/ESA Solar Orbital mission, which together will study our Sun's atmosphere with unprecedented detail. This white paper outlines the current paradigm for ground-based solar synoptic observations, and indicates those areas that will benefit from focused attention

Meta-Analysis Reveals Both the Promises and the Challenges of Clinical Metabolomics

Clinical metabolomics is a rapidly expanding field focused on identifying molecular biomarkers to aid in the efficient diagnosis and treatment of human diseases. Variations in study design, metabolomics methodologies, and investigator protocols raise serious concerns about the accuracy and reproducibility of these potential biomarkers. The explosive growth of the field has led to the recent availability of numerous replicate clinical studies, which permits an evaluation of the consistency of biomarkers identified across multiple metabolomics projects. Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of cancer-related death and has the lowest five-year survival rate primarily due to the lack of an early diagnosis and the limited treatment options. Accordingly, PDAC has been a popular target of clinical metabolomics studies. We compiled 24 PDAC metabolomics studies from the scientific literature for a detailed meta-analysis. A consistent identification across these multiple studies allowed for the validation of potential clinical biomarkers of PDAC while also highlighting variations in study protocols that may explain poor reproducibility. Our meta-analysis identified 10 metabolites that may serve as PDAC biomarkers and warrant further investigation. However, 87% of the 655 metabolites identified as potential biomarkers were identified in single studies. Differences in cohort size and demographics, p-value choice, fold-change significance, sample type, handling and storage, data collection, and analysis were all factors that likely contributed to this apparently large false positive rate. Our meta-analysis demonstrated the need for consistent experimental design and normalized practices to accurately leverage clinical metabolomics data for reliable and reproducible biomarker discovery

Potential Metabolite Biomarkers of Multiple Sclerosis from Multiple Biofluids

Multiple sclerosis (MS) is a chronic and progressive neurological disorder without a cure, but early intervention can slow disease progression and improve the quality of life for MS patients. Obtaining an accurate diagnosis for MS is an arduous and error-prone task that requires a combination of a detailed medical history, a comprehensive neurological exam, clinical tests such as magnetic resonance imaging, and the exclusion of other possible diseases. A simple and definitive biofluid test for MS does not exist but is highly desirable. To address this need, we have employed NMR-based metabolomics to identify potentially unique metabolite biomarkers of MS from a cohort of age and sex matched samples of cerebrospinal fluid (CSF), serum, and urine from 206 progressive multiple sclerosis (PMS) patients, 46 relapsing remitting multiple sclerosis (RRMS) patients, and 99 healthy volunteers without an MS diagnosis. We identified 32 metabolites in CSF that varied between control and PMS patients. Utilizing patient matched serum samples, we were able to further identify 31 serum metabolites that may serve as biomarkers for PMS patients. Lastly, we identified 14 urine metabolites associated with PMS. All potential biomarkers are associated with metabolic processes linked to the pathology of MS such as demyelination and neuronal damage. Four metabolites with identical profiles across all three biofluids were discovered, which demonstrates their potential value as cross-biofluid markers of PMS. We further present a case for using metabolic profiles from PMS patients to delineate biomarkers of RRMS. Specifically, three metabolites exhibited a variation from healthy volunteers without MS through RRMS and PMS patients. The consistency of metabolite changes across multiple biofluids combined with the reliability of a ROC classification may provide a rapid diagnostic test for MS

Improving prescribing practices with rapid diagnostic tests (RDTs): synthesis of 10 studies to explore reasons for variation in malaria RDT uptake and adherence.

OBJECTIVES: The overuse of antimalarial drugs is widespread. Effective methods to improve prescribing practice remain unclear. We evaluated the impact of 10 interventions that introduced rapid diagnostic tests for malaria (mRDTs) on the use of tests and adherence to results in different contexts. DESIGN: A comparative case study approach, analysing variation in outcomes across different settings. SETTING: Studies from the ACT Consortium evaluating mRDTs with a range of supporting interventions in 6 malaria endemic countries. Providers were governmental or non-governmental healthcare workers, private retail sector workers or community volunteers. Each study arm in a distinct setting was considered a case. PARTICIPANTS: 28 cases from 10 studies were included, representing 148 461 patients seeking care for suspected malaria. INTERVENTIONS: The interventions included different mRDT training packages, supervision, supplies and community sensitisation. OUTCOME MEASURES: Analysis explored variation in: (1) uptake of mRDTs (% febrile patients tested); (2) provider adherence to positive mRDTs (% Plasmodium falciparum positive prescribed/given Artemisinin Combination Treatment); (3) provider adherence to negative mRDTs (% P. falciparum negative not prescribed/given antimalarial). RESULTS: Outcomes varied widely across cases: 12-100% mRDT uptake; 44-98% adherence to positive mRDTs; 27-100% adherence to negative mRDTs. Providers appeared more motivated to perform well when mRDTs and intervention characteristics fitted with their own priorities. Goodness of fit of mRDTs with existing consultation and diagnostic practices appeared crucial to maximising the impact of mRDTs on care, as did prior familiarity with malaria testing; adequate human resources and supplies; possible alternative treatments for mRDT-negative patients; a more directive intervention approach and local preferences for ACTs. CONCLUSIONS: Basic training and resources are essential but insufficient to maximise the potential of mRDTs in many contexts. Programme design should respond to assessments of provider priorities, expectations and capacities. As mRDTs become established, the intensity of supporting interventions required seems likely to reduce

Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer

Introduction: MicroRNAs (miRs) are interesting new diagnostic targets that may provide important insights into the molecular pathogenesis of breast cancer. Here we evaluated, for the first time, the feasibility and clinical utility of circulating miRs as biomarkers for the detection and staging of breast cancer. Methods: The relative concentrations of breast cancer-associated miR10b, miR34a, miR141 and miR155 were measured in the blood serum of 89 patients with primary breast cancer (M0, n = 59) and metastatic disease (M1, n = 30), and 29 healthy women by a TaqMan MicroRNA Assay. Results: The relative concentrations of total RNA (P = 0.0001) and miR155 (P = 0.0001) in serum significantly discriminated M0-patients from healthy women, whereas miR10b (P = 0.005), miR34a (P = 0.001) and miR155 (P = 0.008) discriminated M1-patients from healthy controls. In breast cancer patients, the changes in the levels of total RNA (P = 0.0001), miR10b (P = 0.01), miR34a (P = 0.003) and miR155 (P = 0.002) correlated with the presence of overt metastases. Within the M0-cohort, patients at advanced tumor stages (pT3 to 4) had significantly more total RNA (P = 0.0001) and miR34a (P = 0.01) in their blood than patients at early tumor stages (pT1 to 2). Conclusions: This pilot study provides first evidence that tumor-associated circulating miRs are elevated in the blood of breast cancer patients and associated with tumor progression

Exploring the trilemma of cost-efficiency, landscape impact and regional equality in onshore wind expansion planning

Onshore wind development has historically focused on cost-efficiency, which may lead to uneven turbine distributions and public resistance due to landscape impacts. Using a multi-criteria planning approach, we show how onshore wind capacity targets can be achieved by 2050 in a cost-efficient, visually unobtrusive and evenly distributed way. For the case study of Germany, we build on the existing turbine stock and use open data on technically feasible turbine locations and data on scenicness of landscapes to plan the optimal expansion. The analysis shows that while the trade-off between optimizing either cost-efficiency or landscape impact of the turbines is rather weak with about 15% higher costs or scenicness, an even distribution has a large impact on these criteria. However, a more evenly distributed expansion is necessary for the achievement of the targeted south quota, a policy target that calls for more wind turbine additions in southern Germany. Our analysis assists stakeholders in resolving the onshore wind expansion trilemma

Locomotor Adaptation to Resistance During Treadmill Training Transfers to Overground Walking in Human SCI

Treadmill training has been used as a promising technique to improve overground walking in patients with spinal cord injury (SCI). Previous findings showed that a gait pattern may adapt to a force perturbation during treadmill training and show aftereffects following removal of the force perturbation. We hypothesized that aftereffects would transfer to overground walking to a greater extent when the force perturbation was resisting rather than assisting leg swing during treadmill training. Ten subjects with incomplete SCI were recruited into this study for two treadmill training sessions: one using swing resistance and the other using swing assistance during treadmill stepping. A controlled resistance/assistance was provided to the subjects’ right knee using a customized cable-driven robot. The subjects’ spatial and temporal parameters were recorded during the training. The same parameters during overground walking were also recorded before and after the training session using an instrumented walkway. Results indicated that stride length during treadmill stepping increased following the release of resistance load and the aftereffect transferred to overground walking. In contrast, stride length during treadmill stepping decreased following the release of assistance load, but the aftereffect did not transfer to overground walking. Providing swing resistance during treadmill training could enhance the active involvement of the subjects in the gait motor task, thereby aiding in the transfer to overground walking. Such a paradigm may be useful as an adjunct approach to improve the locomotor function in patients with incomplete SCI